A diagnostic feature of human cancer cells is the presence of chromosomal abnormalities, yet the significance of karyotypic alterations is not clear. Specifically, it has not been demonstrated that chromosomal rearrangement has any causal role in the formation of human tumor cells although there have been some suspicious correlations of specific cancers with specific chromosomal aberrations. A mechanism by which chromosomal changes might influence a cell in a progressive way would be to affect the manner in which DNA is replicated. It is known that there is a temporal order to DNA replication early in S phase and other classes consistently replicating at later times. We propose to determine whether chromosomal rearrangements alter this temporal order of DNA synthesis. A specific gene of human cells, the genes coding for the 5S ribosomal RNA, has been selected for this study because the genes are repeated yet clustered at a major location on a single chromosome and specific chromosomal rearrangements of this region are available. The time of replication of the 5S genes in normal human cells, in human tumor cells, and in human cells with chromosomal rearrangements will be compared to determine if the chromosomal location of a gene has any influence on its time of replication during S phase.